Modulating Selectivity in Nanogap SensorsHamid Reza Zafarani,† Klaus Mathwig,‡ Serge G. Lemay,§ Ernst J. R. Sudholter,† and Liza Rassaei*,†
†Laboratory of Organic Materials and Interfaces, Department of Chemical Engineering, Delft University of Technology, Van derMaasweg 9, 2629 HZ Delft, The Netherlands‡Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, P.O. Box 196, 9700 AD Groningen,The Netherlands§MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
*S Supporting Information
ABSTRACT: Interference or crosstalk of coexisting redoxspecies results in overlapping of electrochemical signals, and itis a major hurdle in sensor development. In nanogap sensors,redox cycling between two independently biased workingelectrodes results in an amplified electrochemical signal and anenhanced sensitivity. Here, we report new strategies for selectivesensing of three different redox species in a nanogap sensor of a 2fL volume. Our approach relies on modulating the electrodepotentials to define specific potential windows between the twoworking electrodes; consequently, specific detection of each redox species is achieved. Finite element modeling is employed tosimulate the electrochemical processes in the nanogap sensor, and the results are in good agreement with those of experiments.
Selective detection of redox species is important in variousfields such as pharmacy,1−3 pathology,4,5 health,6−8 and
environmental monitoring.9,10 Interference or crosstalk ofcoexisting compounds leads to the overlap of electrochemicalresponses and is one major drawback of these techniques;frequently encountered, it impedes simultaneous detection ofspecies and limits the selectivity of electrochemical sensors.11,12
Thus, many research efforts have been devoted to overcomingthis hurdle, for example, by electrochemically pretreatingelectrodes;13 using different electrode materials;14 modifyingelectrodes with organic compounds,15,16 polymers,17,18 ornanoparticles;10,19,20 adding complexing agents to the sol-ution;21 or by using a combination of these methods.22,23
Sensing redox species using dual electrodes benefits fromamplified electrochemical signals and enhanced sensitivity whilethe contribution from the background current is mini-mized.24,25 In such systems, one electrode is biased at thereduction potential and the other at the oxidation potential.Here, the redox-active species undergo successive oxidation andreduction reactions as they travel by diffusion between theseclosely spaced electrodes. Hence, the Faradaic current isamplified and the sensitivity is enhanced. Interdigitatedelectrodes (IDE)as one of the well-known classes of dualelectrode systemshave been widely used in differentstudies.26−28 IDEs consist of a pair of comb-shaped opposingelectrodes with interlocking teeth in which each set ofelectrodes can be independently biased.A newer type of dual electrode systems is the electrochemical
nanofluidic devices which consist of two planar parallelelectrodes closely spaced (<100 nm) from each other in a
nanofluidic channel.29−31 The interferences in these nanogapdevices29,32,33 have mainly been eliminated by biasing oneelectrode at the potential that consumes the interference whilethe other electrode is swept to quantify the target analyte.34,35
The nanogap is depleted from interfering irreversible redoxspecies and the signal for the analyte is insensitive to theinterfering species. However, this method only eliminates theresponse from interfering irreversible redox species. Therefore,a more versatile technique is required to overcome theinterferences from reversible redox species in these nanogapsensors.In the present work, we introduce a new method to
selectively detect three reversible redox species in the nanogapsensors. The method relies on modulating the potentials ofboth electrodes in a way that each species is separately detected.We implement this method for the simultaneous detection ofthese three species in three different ways unique to dual-electrode sensors: (a) by cyclic voltammetry and varying thefixed potential of the second working electrode; (b) bydifferential cyclic voltammetry (DCV);36,37 and (c) by potentialstep chronoamperometry. Finite element analysis (COMSOLMultiphysics) is employed to model the electrochemicalprocesses in the nanogap sensor and compare with those ofexperiments.
Received: September 2, 2016Accepted: October 26, 2016Published: October 26, 2016
hexaammineruthenium(III) chloride, Ru(NH3)6Cl3, and potassiumiodide, KI, as electroactive model compounds; potassium chloride,KCl, and standard chromium etchant were purchased from Sigma-Aldrich. All solutions were freshly prepared in Milli-Q water with 1 MKCl as supporting electrolyte and the experiments were carried out atroom temperature.Nanogap Device Fabrication. Nanogap devices were fabricated
on a silicon wafer covered with 500 nm thermally grown SiO2,employing several lithography steps and evaporation as previouslyreported.30 In brief, a nanogap device consisted of a platinum bottomelectrode of a 22 μm by 3 μm surface area and a top electrode of 10μm by 9 μm. A 70-nm-thick sacrificial chromium layer between thesetwo electrodes defined the volume of the nanochannel. The wholedevice was covered in a 500 nm silicon oxide/silicon nitridepassivation layer in which access holes to the chromium layer weredry etched. Before measurements, the chromium layer was etchedaway using chromium etchant leaving behind a nanogap sensor. Aschematic and optical micrograph of a nanogap device are presented inFigure 1A and B.Electrochemical Measurements. Electrochemical experiments
were carried out using a Keithley 4200 parameter analyzer with twosource measurement units (SMUs). The SMUs were used as voltagesource and current detection elements to separately bias bothelectrodes and measure faradic currents. A commercial Ag/AgClelectrode (BASi Inc.) was used as a reference, positioned in a reservoiron top of the nanogap device.Numerical Methods. Two-dimensional finite element analysis was
carried out using COMSOL Multiphysics to simulate the electro-chemical processes in the nanochannel with conditions similar to thosefor the experimental measurements.38 Assuming a highly concentratedsupporting electrolyte and an unstirred solution, diffusion wasconsidered as the only mass transport mechanism in the nanogapsensor as described by Fick’s second law:
∂∂
= ∇C
tD Cj
j j2
(1)
Here, Cj and Dj are the concentration and diffusion coefficient of aredox species j, respectively. The currents are defined based onButler−Volmer kinetics:39
= −i F c k c k[ ]O f R b (2)
α=
− −⎡⎣⎢
⎤⎦⎥k k
F E ERT
exp( )
fh
0(3)
α=
− −⎡⎣⎢
⎤⎦⎥k k
F E ERT
exp(1 ) ( )
bh
0(4)
Here, i is the current, k0 is the mass transfer coefficient, α the chargetransfer coefficient, F the Faraday constant, E the electrode potential,Eh the redox potential of the redox couple, kf and kb are the forward(reduction) and backward (oxidation) rate constants of a redoxreaction, R is the gas constant, T the temperature, cO and cR are theconcentration of oxidized and reduced species, respectively.
Table 1 lists constants used in the simulations, including diffusioncoefficients D and redox potentials (vs Ag/AgCl), Eh, for theFc(MeOH)2, KI, and Ru(NH3)6Cl3 redox couples. An identical rateconstant k0 and transfer coefficients α were assumed for all species.
■ RESULTS AND DISCUSSIONAmplification Factor. Figure 1C shows the cyclic
voltammograms obtained from the redox cycling of 0.33 mM1,1′-ferrocene dimethanol in 1 M potassium chloride in thenanogap sensor. The inset in this figure presents the cyclicvoltammogram obtained in single mode: only the top electrodewas swept and the bottom electrode was left floating. Identicalmeasurements were carried out for Ru(NH3)6Cl3 andpotassium iodide (see Figure S1 in the SupportingInformation). Comparing the limiting currents in these twomodes, Idual/Isingle, leads to an amplification factor of 170corresponding to a gap height of 74 nm according to33
Figure 1. (A) Schematic view of the nanogap device. (B) Optical micrograph of a nanogap sensor (top view). (C) Cyclic voltammogram of 0.33 mMFc(MeOH)2 in 1 M KCl solution. The top electrode was swept between 0 and 0.5 V (vs Ag/AgCl) at a 10 mV s−1 scan rate while the bottomelectrode was kept at 0 V. The inset figure shows a cyclic voltammogram in single mode; the top electrode was swept vs Ag/AgCl while the bottomelectrode was kept floating.
Table 1. Parameters Used in the SimulationProcesses30,37,40−42
where I is limiting Faradaic current for two planar electrodes inclose distance, n is the number of electrons transferred in theredox reaction, A is the overlapping area between the twoelectrodes, and z is the distance between the electrodes, i.e., thenanochannel height.Tuning Electrodes’ Potentials for Separate Detection
of Each Species. Conventional electrochemical measurementssuffer from poor selectivity, because, in a mixture of variousreduced (or oxidized) electroactive species having differentstandard redox potentials, all species are simultaneouslyoxidized (or reduced) when a high (or low) enough electrodepotential is applied. The interferences caused this waycomplicate the interpretation of the results as the electro-oxidation (or electro-reduction) current for the redox specieswith the highest oxidation (or lowest reduction) potential issuperimposed by the signals from the other redox species.Nanogap sensors not only allow amplifying the electro-
chemical signals of redox species, but also open up thepossibility to prevent such interferences. The two workingelectrodes in the nanogap sensor are independently biased and,thus, they enable selective electrochemical reactions of specificredox couples. Selective detection is achieved by defining thepotentials of the two electrodes in a way in which only thetarget species undergoes redox cycling. Simultaneously,interfering species are also reduced or oxidized but they donot undergo redox cycling, and therefore, the signal of thesespecies is not amplified.Figure 2 shows cyclic voltammograms for a mixture of 0.33
mM Fc(MeOH)2, 0.33 mM Ru(NH3)63+ and 0.33 mM I− as
three redox active species in 1 M KCl solution. Varying thebottom electrode potential to certain fixed potentials leads to aseparate detection of these species in specific potential ranges.Here, the top electrode is swept between −0.33 and 0.8 V (vsAg/AgCl) while the potential of the bottom electrode is kept at−0.3, 0, and 0.4 V, respectively.In Figure 2A, the potential of the bottom electrode is set at
−0.3 V. As presented, the potential of the top electrode isscanned from −0.3 V, and the first current plateau correspondsto redox cycling of Ru(NH3)6
3+/2+ ions (Eh = −0.16 V) withoutany interference from the other two species; the second currentplateau relates to the combined redox cycling of Fc-(MeOH)2
0/+1 (Eh = 0.26 V) and Ru(NH3)63+/2+ ions. The
third current plateau associates with the redox cycling of I− (Eh
= 0.54 V) and the previous two species. The redox reactions ofthe species are as follows:
⇄ ++ −Fc(MeOH) Fc(MeOH) e2 2 (6)
+ ⇄+ − +Ru(NH ) e Ru(NH )3 63
3 62
(7)
⇄ +− −I 1/2I e2 (8)
Once the potential of the bottom electrode is changed to 0 V(see Figure 2B), the interference and the contribution ofRu(NH3)6
3+/2+ ions on redox cycling of Fc(MeOH)20/+1 and
I− disappears. As presented in this figure, here, redox cycling ofRu(NH3)6
3+/2+ occurs in the potential window of −0.3 to−0.16 V. For potentials above −0.16 V, Ru(NH3)6
3+/2+ ionsexist in the oxidized form and cannot undergo redox cyclinganymore. Hence, their contribution to the redox cyclingcurrents of Fc(MeOH)2
0/+1 and I− is eliminated. This allowsdetection of the signal of Fc(MeOH)2
0/+1 (second currentplateau) without any Ru(NH3)6
3+/2+ interference in thispotential range. Notwithstanding, the third current plateaustill suffers from the interference of Fc(MeOH)2
0/+1, and theredox cycling current of I− is superimposed by Fc(MeOH)2
0/+1.In order to resolve this issue, the potential of the bottomelectrode is next set at 0.4 V (Figure 2C). Here, for potentialsabove 0.26 V, only I− can undergo redox cycling (third currentplateau) and the signal is free from any interferences of bothFc(MeOH)2
0/+1 and Ru(NH3)63+/2+. Note that at potentials
above 0.26 V in Figure 2C, Fc(MeOH)20/+1 is constantly
oxidized at both electrodes, but it does not undergo redoxcycling; this leads to a negligible current contribution (resultingto a deviation of 0.16%) compared to the amplified redoxcycling current.Using eq 5 and the constants in Table 1, the expected
limiting currents are estimated to be 11 nA, 9 nA, and 30 nA forRu(NH3)6
3+/2+, Fc(MeOH)20/+1, and I−, respectively, in good
agreement with those obtained from experimental measure-ments (see Figure 2). The 30 nA oxidation current obtained forI− (also presented in Figure 2C) indicates that this process isoverall a one-electron transfer reaction in agreement withprevious reports.43−45 The hysteresis observed during theoxidation of iodide is caused by a pronounced desorption ofiodide ions from the electrode surface during the forward scanand subsequent adsorption after the potential reversal.46
Differential Cyclic Voltammetry of Redox Species inthe Nanogap Sensor. We employ the method of differentialcyclic voltammetry37 to directly visualize the separate sensing ofall species in a single potential sweep. Here, the potentials of
Figure 2. Cyclic voltammetry of a mixture of 0.33 mM Ru(NH3)63+, 0.33 mM Fc(MeOH)2, and 0.33 mM I− in a 1 M KCl solution. The top
electrode is swept between −0.33 and 0.8 V at a scan rate of 10 mV s−1, and the bottom electrode potential is fixed at (A) −0.3 V, (B) 0 V, and (C)0.4 V. Arrows (A) indicate the scan direction.
both electrodes are simultaneously swept with a constant offset.We define various potential windows of 10 mV, 25 mV, 50 mV,and 100 mV between the two working electrodes in the samemixture solution of 0.33 mM Fc(MeOH)2, 0.33 mM Ru-(NH3)6
3+, and 0.33 mM I− in 1 M aqueous KCl. Once thesepotential windows are defined, a clear peak current is obtainedfor each redox species. The peak potential for each speciescorresponds to its redox potential.Figure 3 shows the redox cycling currents obtained as a
function of the mean potential between the top and bottom
electrodes and a clear separation of all species. Due to thesimultaneous sweep of both electrodes, the resulting currentshave a differential nature. The peak currents at the half-wavepotential of each species correspond to ΔI/ΔE as well as to thespecies’ concentration. As shown in Figure 3, a narrowerpotential window leads to a lower current but a betterseparation of species. For example, for a potential window of 10mV, a peak current of 1.12 nA is obtained for Fc(MeOH)2
0/+1
species, while for a 100 mV potential window, the current peaksat 7.8 nA. However, the full width at half-maximum (fwhm)increases from 92 mV for a 10 mV potential window to 125 mVfor a 100 mV potential window. Therefore, a wider potentialwindow limits how well the redox species are separated; thebaseline distance between Fc(MeOH)2
0/+1 peak and adjacentpeaks is decreased by applying a wider potential window. Thewidest potential window that can be applied depends on thedifference in the redox potentials of species. For example, thelargest potential window for separate detection of Fc-(MeOH)2
0/+1 and I− is 280 mV corresponding to Eh,I− −
Eh,Fc(MeOH)2 = 280 mV (more details are presented in Figure S2in the Supporting Information).Chronoamperometric Detection of Redox Species in
the Nanogap Sensor. In the two voltammetry schemesdescribed above, the discriminatory power of specific electrodebiases for both electrodes is shown in a direct way. However,the separate detection of analytes plays out its full advantage inchronoamperometric sensing with fixed potentials, in whichredox waves of potential interfering species are not visible. Weemployed chronoamperometry in the nanogap sensor. Here,the device is filled with a mixture of 0.4 mM KI and 0.6 mMFc(MeOH)2 in 1 M KCl solution. A constant potential of 0.4 Vvs Ag/AgCl is applied to the top electrode while the potential
of the bottom electrode is stepped between 0.1 and 0.4 V andthen between 0.4 and 0.7 V (see Figure 4).
Once the potential of the bottom electrode is stepped to 0.1V, Fc(MeOH)2 undergoes redox cycling (first two steps)without any interference from I−. Here, Fc(MeOH)2 isconstantly oxidized at the top electrode and reduced at thebottom electrode. Similarly, when the bottom electrodepotential is stepped to 0.7 V, I− ions undergo redox cyclingwithout any interference from Fc(MeOH)2
0/+1. I− is constantlyoxidized at the bottom electrode and reduced at the topelectrode. At the same time, Fc(MeOH)2
0/+1 is constantlyoxidized at both top and bottom electrodes, but since theycannot undergo redox cycling, their contribution to the currentfor I− is negligible (resulting in a deviation of 0.3%). Theseresults are in good agreement with those obtained from cyclicvoltammetry. The long transient time for I− is due to thedynamic adsorption at the Pt electrode surfaces.46−48
Numerical Analysis. Figure 5 shows the comparison ofcyclic voltammetry as well as differential cyclic voltammetry of0.33 mM Ru(NH3)6
3+, 0.33 mM Fc(MeOH)2, and 0.33 mM I−
in 1 M KCl for experimental measurements and finite elementsimulation results. Figure 5 A presents the simulated data andits comparison with experimental cyclic voltammograms; here,the top electrode potential is swept between −0.33 and 0.8 V(vs Ag/AgCl) and the bottom electrode potential is kept at−0.3 V. Figure 5 B presents differential cyclic voltammogramsfor the potential window of 100 mV for both experimental andmodeled results. As depicted, simulated data match well withexperimental data. However, a hysteresis is observed exper-imentally for the oxidation and reduction of I− due topronounced adsorption of I−,46 which has not been consideredin the simulations.
■ CONCLUSIONWe proposed a novel strategy for the separate detection ofredox active species in nanogap sensors and implemented it inthree ways: first, by tuning the electrode potentials only desiredspecies undergo redox cycling; hence, the obtained current isfree of any interferences (shown for both cyclic voltammetryand chronoamperometric measurements). Second, by defininga potential window between the two electrodes and
Figure 3. Differential cycling voltammetry in the nanogap sensor. Thetop and bottom electrodes are swept (vs Ag/AgCl) at a scan rate of 10mV s−1 with a constant potential difference ranging from 10 mV to100 mV. The limiting currents are shown as a function of meanpotential between the two electrodes.
Figure 4. Chronoamperometry results obtained for a mixture of 0.6mM Fc(MeOH)2 and 0.4 mM KI in 1 M KCl solution. The insetshows the applied potentials as a function of time. The top electrode iskept at constant potential of 0.4 V and the bottom electrode is steppedto 0.1, 0.4, or 0.7 V.
simultaneously sweeping them, each species can individuallyundergo redox cycling. Third, by chronoamperometry specificconcentrations can be monitored without interference by usinga matching potential window. A good agreement was obtainedbetween the experimental and simulation results. Thetechniques introduced in this study may lead to new ways forthe selective detection of redox species in nanogap devices.
■ ASSOCIATED CONTENT*S Supporting InformationThe Supporting Information is available free of charge on theACS Publications website at DOI: 10.1021/acssen-sors.6b00556.
NotesThe authors declare no competing financial interest.
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